What is the treatment approach for a patient with a urinary tract infection (UTI) caused by Staphylococcus, Enterococcus (E.) faecalis, Klebsiella pneumoniae, or Ureaplasma?

Treatment of UTIs Caused by Staphylococcus, E. faecalis, Klebsiella pneumoniae, and Ureaplasma

For UTIs caused by these specific organisms, treatment must be tailored to the pathogen identified on culture, with first-line agents including fosfomycin or nitrofurantoin for E. faecalis, cephalosporins or carbapenems for Klebsiella pneumoniae, beta-lactams for Staphylococcus, and doxycycline for Ureaplasma, with treatment duration of 7-14 days depending on whether the infection is complicated. 1, 2

Initial Assessment and Culture Requirements

Before initiating treatment, obtain urine culture and antimicrobial susceptibility testing in all cases. 1 These organisms represent a more complex microbial spectrum than typical uncomplicated UTIs, and antimicrobial resistance is more likely. 1

Determine if the UTI is complicated or uncomplicated, as this fundamentally changes management:

• Complicated UTI factors include male gender, obstruction, foreign body (catheter), incomplete voiding, diabetes, immunosuppression, healthcare-associated infection, or multidrug-resistant organisms. 1
• Treatment duration and antibiotic selection differ significantly between these categories. 1

Organism-Specific Treatment Recommendations

Enterococcus faecalis

First-line options:

• Fosfomycin 3g oral single dose is the preferred agent due to FDA approval, excellent activity against E. faecalis, and good safety profile even in renal impairment. 2
• Nitrofurantoin 100mg PO four times daily for 5-7 days has good activity against E. faecalis but requires caution in elderly patients with reduced renal function (eGFR <60). 2, 1
• Ampicillin/Amoxicillin if susceptibility is confirmed—ampicillin is the drug of choice for enterococcal infections. 2, 3

Duration: 3-7 days for uncomplicated lower UTI; 7-14 days for complicated UTI (14 days for men when prostatitis cannot be excluded). 1, 2

Avoid fluoroquinolones as empiric therapy due to high resistance rates in enterococci. 2

All E. faecalis isolates historically show sensitivity to ampicillin, and teicoplanin/vancomycin reach high urinary levels if needed for resistant strains. 3

Klebsiella pneumoniae

First-line options for empiric therapy (pending susceptibilities):

• Third-generation cephalosporins IV (e.g., ceftriaxone) for complicated UTI with systemic symptoms. 1
• Cefepime 1-2g IV every 8-12 hours is FDA-approved for UTIs caused by K. pneumoniae, particularly for severe infections. 4
• Oral options (if mild-moderate and susceptible): Cefpodoxime 200mg twice daily for 10 days or ceftibuten 400mg daily for 10 days. 1

For ESBL-producing K. pneumoniae:

• Carbapenems (meropenem or imipenem) are the treatment of choice. 1
• Fourth-generation cephalosporins (cefepime) may be used if ESBL is absent. 1

Duration: 7-10 days for uncomplicated; 7-14 days for complicated UTI. 1, 4

Important caveat: Resistance to cephalosporins in Klebsiella has increased over time, particularly to first and second-generation agents. 5 Always tailor therapy based on susceptibility results. 1

Staphylococcus species

For Staphylococcus aureus (methicillin-susceptible):

• Cefepime 2g IV every 12 hours for 10 days is FDA-approved for uncomplicated skin/soft tissue infections and can be used for UTIs. 4
• First-generation cephalosporins or anti-staphylococcal penicillins if susceptible. 1

For Staphylococcus saprophyticus (common in young women):

• Treat as uncomplicated cystitis with nitrofurantoin, TMP-SMX, or fosfomycin based on local resistance patterns. 1

Duration: 7 days for uncomplicated; 10-14 days for complicated UTI. 1

Ureaplasma urealyticum

First-line treatment:

• Doxycycline 100mg PO twice daily is FDA-approved for nongonococcal urethritis caused by Ureaplasma urealyticum. 6

Duration: 7 days is standard for urogenital Ureaplasma infections. 6

Ureaplasma is inherently resistant to beta-lactams due to lack of cell wall, making tetracyclines the drug of choice. 6

Treatment Algorithm Based on Clinical Presentation

Uncomplicated UTI (non-pregnant women, no structural abnormalities)

1. Obtain urine culture before starting antibiotics. 1
2. Initiate organism-specific therapy as outlined above.
3. Treatment duration: 3-7 days (5-7 days preferred for most agents). 1
4. No routine post-treatment cultures if asymptomatic. 1

Complicated UTI (males, structural abnormalities, catheter, immunosuppression)

1. Obtain urine culture and blood cultures if systemically ill. 1
2. For systemic symptoms/sepsis, start IV empiric therapy:
   • Amoxicillin plus aminoglycoside, OR
   • Second-generation cephalosporin plus aminoglycoside, OR
   • Third-generation cephalosporin IV. 1
3. Tailor therapy once culture results available.
4. Treatment duration: 7-14 days (14 days for men when prostatitis cannot be excluded). 1
5. Address underlying complicating factors (remove catheter if possible, relieve obstruction). 1, 2

Catheter-Associated UTI

1. Remove or replace catheter if feasible—this is critical for cure. 1, 2
2. Treat only if symptomatic (fever, rigors, altered mental status, flank pain, pelvic discomfort). 1
3. Do not treat asymptomatic bacteriuria in catheterized patients. 1
4. Duration: 7 days if catheter removed; 10-14 days if catheter must remain. 1

Special Considerations for Renal Impairment

With reduced eGFR, dose adjustments are necessary:

• Nitrofurantoin: Use with caution if eGFR <60; avoid if eGFR <30. 2
• Fosfomycin: No dose adjustment needed, making it ideal for renal impairment. 2
• Cefepime: Requires dose reduction based on creatinine clearance. 4
• Doxycycline: No dose adjustment required. 6

Resistance Patterns and Antibiotic Stewardship

Key resistance trends:

• E. coli resistance to fluoroquinolones has increased significantly after 2000. 5
• Klebsiella shows decreasing susceptibility to some cephalosporins and carbapenems. 5, 7
• Male gender and older age are risk factors for resistance in K. pneumoniae to multiple agents. 7

Avoid these common pitfalls:

• Do not treat asymptomatic bacteriuria—this fosters resistance and increases recurrent UTI episodes. 1, 2
• Do not use fluoroquinolones empirically if local resistance exceeds 10% or patient has used them in past 6 months. 1, 2
• Do not prolong therapy beyond necessary duration—this increases resistance and adverse effects. 1, 2
• Do not ignore susceptibility testing—empiric therapy must be tailored once results available. 1, 2

When to Consider Alternative or Salvage Therapy

If first-line treatments fail or for multidrug-resistant organisms:

• Linezolid 600mg IV/PO every 12 hours for resistant enterococci (reserve for severe infections). 2
• Daptomycin 6-12mg/kg IV daily for complicated UTIs when other options fail. 2
• Carbapenems for ESBL-producing organisms. 1
• Polymyxins, tigecycline, or fosfomycin for carbapenem-resistant Enterobacteriaceae. 1

Follow-Up and Treatment Failure

If symptoms persist despite appropriate therapy:

• Obtain repeat urine culture to assess for resistance or alternative pathogen. 1, 2
• Differentiate between colonization and true infection—pyuria and symptoms must be present. 2
• Consider imaging if bacterial persistence occurs (calculi, abscess, obstruction). 1
• Retreat with 7-day course using different agent based on susceptibilities. 1